Summary/Abstract Chronic lower respiratory disease (CLRD), which includes chronic obstructive pulmonary disease (COPD) and asthma, is now the third leading cause of death globally. COPD, which is defined by airflow obstruction on spirometry, is a rising cause of years of life lost and disability-adjusted life years in the United States (US). Cigarette smoking, which accelerates lung function decline, is the major risk factor for CLRD. Noncigarette tobacco use, including cigars and pipes, is frequently perceived as low risk compared to cigarettes; however, concentrations of certain toxic chemicals from cigar and pipe smoking are comparable to ? and, in some instances, higher than ? those from cigarette smoking. This application will test if, like cigarette use, noncigarette tobacco use is associated with accelerated lung function decline and incident clinical CLRD events. We will test these hypotheses in the NHLBI Pooled Cohorts Study, which has harmonized and pooled data from 9 US general population-based cohorts that collected lung function data in 65,251 American Indian, Asian, Black, Hispanic and White adult men and women. Our investigative group has rigorously quality- controlled lung function measures across the cohorts using contemporary standards, yielding 105,696 valid spirometry exams. We have also developed and validated definitions for incident asthma- and COPD-related hospitalizations and deaths, of which there are presently >3,900 events over >340,000 person-years of follow- up. In Aim 1, we will harmonize cigar and pipe exposures across cohorts. These exposures were ascertained from standardized questionnaires and will be systematically evaluated, quality-controlled, and harmonized using the approach we have already successfully applied for cigarette tobacco exposures. We will use the harmonized data to classify our primary exposure, exclusive cigar/pipe use, defined as ever-use of cigar and/or pipe in lifelong never-cigarette smokers. We will also classify current cigar/pipe use, cumulative cigar/pipe exposure (cigar and pipe years), and current cigar/pipe intensity. In Aim 2, we will test associations between exclusive cigar/pipe use and longitudinal lung function, including decline in FEV1, FVC, and FEV1/FVC, as well as with incident airflow obstruction. In Aim 3, we will test associations with CLRD events. The proposed work will inform our understanding of the relative risks of cigar use and pipe use versus conventional cigarette use and establish the physiologic and clinical significance of cigar/pipe use with respect to chronic lower respiratory disease. These findings, which will be based upon gold standard phenotyping from a large US general population-based sample, will be suitable to inform regulatory decisions regarding cigar and pipe tobacco products.